Clinical and Molecular Effects of Interleukin-17 Pathway Blockade in Psoriasis

February 2020 | Volume 19 | Issue 2 | Original Article | 138 | Copyright © February 2020


Published online January 17, 2020

Lawrence Green , Jeffrey M. Weinberg , Alan Menter , Jennifer Soung , Edward Lain , Abby Jacobson

aGeorge Washington University School of Medicine, Washington, DC bIcahn School of Medicine at Mount Sinai, New York, NY cBaylor Scott & White, Dallas, TX dSouthern California Dermatology, Santa Ana, CA eAustin Institute for Clinical Research, Pflugerville, TX fOrtho Dermatologics, Bridgewater, NJ

associated with an increased risk of malignancy and may be used in patients with hepatitis B or C infections.45 As shown in Table 1, the rates of serious adverse events with brodalumab, secukinumab, and ixekizumab ranged from 1.0% to 1.8%, comparable to the rates reported with placebo.29,37-40 The most common adverse events reported with these agents included nasopharyngitis, upper respiratory tract infection, headache, and arthralgia.29,37,38

In a systematic review of clinical trials of patients with psoriasis or psoriatic arthritis, Candida infections were reported in 4.0% of patients treated with brodalumab, 1.7% of patients treated with secukinumab, and 3.3% of patients treated with ixekizumab compared with 0.3%, 2.3%, and 0.8% in those receiving placebo, ustekinumab, or etanercept, respectively.46 The majority of Candida infections in anti–IL-17 biologic clinical trials occurred in the oral cavity and were of mild severity.47 Exacerbation of IBD has also been reported in trials of anti– IL-17 agents in psoriasis, including 1 case of Crohn disease with brodalumab.48 In a study of ixekizumab, incidence rates of Crohn disease and ulcerative colitis were 0.10 and 0.20 per 100 patient-years, respectively, and were 0.11 and 0.15 per 100 patient-years, respectively, in a study of secukinumab.48 On the basis of these observations, caution should be used in patients with possible or diagnosed IBD.48

SUMMARY

The IL-17 pathway plays a crucial role in the immunopathogenesis and development of psoriasis. Currently, 3 US Food and Drug Administration–approved agents affect this pathway for treatment of psoriasis (brodalumab, secukinumab, and ixekizumab) with others in development (bimekizumab).49 Brodalumab is a highly selective IL-17 receptor A antagonist that blocks multiple downstream inflammatory cytokines that are elevated in psoriasis, including IL-17C and IL-17E, which may correlate with the observed efficacy of brodalumab. Secukinumab and ixekizumab selectively bind to and neutralize only IL-17A. Inhibition of the IL-17 pathway with these agents results in improvements in clinical, histologic, and genetic characteristics of psoriasis. The immunomodulation produced by these agents has been associated with a favorable safety profile. Overall, the clinical improvement and normalization of genetic hallmarks of psoriasis provide a strong case for the unique role of IL-17 receptor blocking as an important therapeutic mechanism of action in treating psoriasis. Understanding the unique mechanisms by which each of these biologics interacts with the IL-17 pathway to inhibit downstream proinflammatory signal cascade will be of benefit to dermatologists in making informed treatment decisions.

DISCLOSURES

Lawrence Green has served as an investigator, consultant, or speaker for Amgen, AbbVie, Bausch Health, Celgene, Sun Pharma, Pharma, Eli Lilly, and Novartis. Jeffrey M. Weinberg serves as an investigator for Boehringer Ingelheim, LEO Pharma, and Novartis and serves as a speaker for and/or advisor to AbbVie, Amgen, Celgene, Eli Lilly, LEO Pharma, and Novartis. Alan Menter has received compensation from or served as an investigator, consultant, advisory board member, or speaker for AbbVie, Allergan, Amgen, Anacor, Boehringer Ingelheim, Celgene, Dermira, Eli Lilly, Galderma, Janssen Biotech, LEO Pharma, Merck, Neothetics, Novartis, Pfizer, Regeneron, Symbio/Maruho, Vitae, and Xenoport. Jennifer Soung has served as an investigator, consultant, advisory board member, or speaker for AbbVie, Actavis, Actelion, Allergan, Amgen, Boehringer Ingelheim, Cassiopeia, Celgene, Dr. Reddy, Eli Lilly, Galderma, GSK, Janssen, Kadmon, LEO Pharma, Menlo, National Psoriasis Foundation (nonprofit), Novan, Novartis, Ortho Dermatologics, Pfizer, Regeneron, and UCB. Edward Lain has received compensation from or served as an investigator, consultant, advisory board member, or speaker for AbbVie, Allergan, Boehringer Ingelheim, Celgene, Dermira, Eli Lilly, Galderma, LEO Pharma, Neothetics, Novartis, Pfizer, Sol-Gel, Endo Pharmaceuticals, Dr Reddy, Kadmon, Thync Global, Cassiopeia, Menlo, UCB, Kiniksa, Glenmark, Sienna, Sebacia, BMS, Vanda, Chemocentryx, Brickell, Aclaris, and Novan. Abby Jacobson is an employee of Ortho Dermatologics and holds stock and/or stock options in Bausch Health.

ACKNOWLEDGMENT

This study was sponsored by Ortho Dermatologics. Editorial assistance was provided under the direction of the authors by Angela Cimmino, PharmD, Rebecca Slager, PhD, and David Boffa, ELS, of MedThink SciCom, with support from Ortho Dermatologics.

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